Background: Injury of a spinal nerve or dorsal root ganglion (DRG) during selective spinal nerve blocks is a potentially serious complication that has not been adequately investigated. Our hypothesis was that local anesthetic injection into these structures may result in an inflammatory response and hyperalgesia. Methods: We evaluated inflammatory and behavioral responses after injection of 4 microL lidocaine or saline into the L5 spinal nerve or DRG of rats after partial laminectomy. Behavioral testing was performed before and after surgery to examine hyperalgesia in response to nociceptive mechanical stimulation of the foot. DRGs were harvested and stained, and rings of immunoreactive glial cells around neurons were counted. Results: Animals demonstrated hyperalgesia on the ipsilateral paw up to 4 days after lidocaine injection into the DRG but not after injection into the spinal nerve. The number of glial fibrillary acid protein immunopositive glial cell rings, which represent activation of satellite cells, significantly increased in DRGs after injection of lidocaine into either the DRG or the spinal nerve. The number of glial fibrillary acid protein-positive cells in the lidocaine-injected group was significantly larger than in the saline-injected group. Sporadic OX-42 immunopositive cells, which represent activated microglia, were also seen in lidocaine-injected DRGs. Testing for Pan-T expression, which labels activated T lymphocytes, showed no positive cells. Conclusions: Lidocaine injection into the DRG may produce hyperalgesia, possibly due to activation of resident satellite glial cells. In a clinical setting, local anesthetic injection into the DRG should be avoided during selective spinal nerve blocks.